How action structures time: About the perceived temporal order of action and predicted outcomes

Few ideas are as inexorable as the arrow of causation: causes must precede their effects. Explicit or implicit knowledge about this causal order permits humans and other animals to predict and control events in order to produce desired outcomes. The sense of agency is deeply linked with representation of causation, since it involves the experience of a self-capable of acting on the world. Since causes must precede effects, the perceived temporal order of our actions and subsequent events should be relevant to the sense of agency. The present study investigated whether the ability to predict the outcome of an action would impose the classical cause-precedes-outcome pattern on temporal order judgements. Participants indicated whether a visual stimulus (dots moving upward or downward) was presented either before or after voluntary actions of the left or right hand. Crucially, the dot motion could be either congruent or incongruent with an operant association between hand and motion direction learned in a previous learning phase. When the visual outcome of voluntary action was congruent with previous learning, the motion onset was more often perceived as occurring after the action, compared to when the outcome was incongruent. This suggests that the prediction of specific sensory outcomes restructures our perception of timing of action and sensory events, inducing the experience that congruent effects occur after participants' actions. Interestingly, this bias to perceive events according to the temporal order of cause and outcome disappeared when participants knew that motion directions were automatically generated by the computer. This suggests that the reorganisation of time perception imposed by associative learning depends on participants' causal beliefs

Quantification of white matter fibre pathways disruption in frontal transcortical approach to the lateral ventricle or the interventricular foramen in diffusion tensor tractography

Pathologies occupying the interventricular foramen (foramen of Monro — FM) or the anterior part of lateral ventricle (LV) are accessed by the transcortical or transcallosal route. As severing of rostral corpus callosum has been deemed inferior to cortical incision, the approaches through various points of frontal lobe have been developed. Superior (F1), middle (F2) frontal gyrus or occasionally superior frontal sulcus are used as an entry of neurosurgical corridor. In spite of the fact that every approach to LV or FM causes its characteristic irreversible damage to white matter, to date all of transcortical routes are regarded as equivalent. The current study compared the damage of main neural bundles between virtualtrans-F1 and trans-F2 corridors by means of diffusion tensor tractography method (DTT) in 11 magnetic resonance imaging (MRI) exams from clinical series (22 hemispheres, regardless of dominance). Corpus callosum, cingulum, subdivisions I and II of superior longitudinal fasciculus (SLF I and SLF II), corticoreticular as well as pyramidal tracts crossing both approaches were subjected to surgical violation. Both approaches served a similar total number of fibres (0.94 to 1.78 [× 103]).Trans-F1 route caused significantly greater damage of total white matter volume(F1: 8.26 vs. F2: 7.16 mL), percentage of SLF I fibres (F1: 78.6% vs. F2: 28.6%)and cingulum (F1: 49.4% vs. F2: 10.6%), whereas trans-F2 route interrupted morecorticoreticular fibres (F1: 4.5% vs. F2: 30.7%). Pyramidal tract (F1: 0.6% vs. F2:1.3%) and SLF II (F1: 15.9% vs. F2: 26.2%) were marginally more vulnerable incase of the access via middle frontal gyrus. Both approaches destroyed 7% of callosal fibres. Summarising the above DTT findings, trans-F2 route disrupted a greater number of fibres from eloquent neural bundles (SLF II, pyramidal and corticoreticular tracts), therefore is regarded as inferior to trans-F1 one. Due to lack of up-to-date guidelines with recommendations of the approaches to LV or FM, an individual preoperative planning based on DTT should precede a surgery

Intentional Binding Is Driven by the Mere Presence of an Action and Not by Motor Prediction

Intentional binding refers to the fact that when a voluntary action produces a sensory outcome, action and outcome are perceived as being closer together in time. This phenomenon is often attributed, at least partially, to predictive motor mechanisms. However, previous studies failed to unequivocally attribute intentional binding to these mechanisms, since the contrasts that have been used to demonstrate intentional binding covered not only one but two processes: temporal control and motor identity prediction. In the present study we aimed to isolate the respective role of each of these processes in the emergence of intentional binding of action-effects. The results show that motor identity prediction does not modulate intentional binding of action-effects. Our findings cast doubts on the assumption that intentional binding of action effects is linked to internal forward predictive process

Action selection and action awareness

Human actions are often classified as either internally generated, or externally specified in response to environmental cues. These two modes of action selection have distinct neural bases, but few studies investigated how the mode of action selection affects the subjective experience of action. We measured the experience of action using the subjective compression of the interval between actions and their effects, known as ‘temporal binding’. Participants performed either a left or a right key press, either in response to a specific cue, or as they freely chose. Moreover, the time of each keypress could either be explicitly cued to occur in one of two designated time intervals, or participants freely chose in which interval to act. Each action was followed by a specific tone. Participants judged the time of their actions or the time of the tone. Temporal binding was found for both internally generated and for stimulus-based actions. However, the amount of binding depended on whether or not both the choice and the timing of action were selected in the same way. Stronger binding was observed when both action choice and action timing were internally generated or externally specified, compared to conditions where the two parameters were selected by different routes. Our result suggests that temporal action–effect binding depends on how actions are selected. Binding is strongest when actions result from a single mode of selection

Protein crystals in adenovirus type 5-infected cells: requirements for intranuclear crystallogenesis, structural and functional analysis

Intranuclear crystalline inclusions have been observed in the nucleus of epithelial cells infected with Adenovirus serotype 5 (Ad5) at late steps of the virus life cycle. Using immuno-electron microscopy and confocal microscopy of cells infected with various Ad5 recombinants modified in their penton base or fiber domains, we found that these inclusions represented crystals of penton capsomers, the heteromeric capsid protein formed of penton base and fiber subunits. The occurrence of protein crystals within the nucleus of infected cells required the integrity of the fiber knob and part of the shaft domain. In the knob domain, the region overlapping residues 489–492 in the FG loop was found to be essential for crystal formation. In the shaft, a large deletion of repeats 4 to 16 had no detrimental effect on crystal inclusions, whereas deletion of repeats 8 to 21 abolished crystal formation without altering the level of fiber protein expression. This suggested a crucial role of the five penultimate repeats in the crystallisation process. Chimeric pentons made of Ad5 penton base and fiber domains from different serotypes were analyzed with respect to crystal formation. No crystal was found when fiber consisted of shaft (S) from Ad5 and knob (K) from Ad3 (heterotypic S5-K3 fiber), but occurred with homotypic S3K3 fiber. However, less regular crystals were observed with homotypic S35-K35 fiber. TB5, a monoclonal antibody directed against the Ad5 fiber knob was found by immunofluorescence microscopy to react with high efficiency with the intranuclear protein crystals in situ. Data obtained with Ad fiber mutants indicated that the absence of crystalline inclusions correlated with a lower infectivity and/or lower yields of virus progeny, suggesting that the protein crystals might be involved in virion assembly. Thus, we propose that TB5 staining of Ad-infected 293 cells can be used as a prognostic assay for the viability and productivity of fiber-modified Ad5 vectors

The prediction of visual stimuli influences auditory loudness discrimination

The brain combines information from different senses to improve performance on perceptual tasks. For instance, auditory processing is enhanced by the mere fact that a visual input is processed simultaneously. However, the sensory processing of one modality is itself subject to diverse influences. Namely, perceptual processing depends on the degree to which a stimulus is predicted. The present study investigated the extent to which the influence of one processing pathway on another pathway depends on whether or not the stimulation in this pathway is predicted. We used an action–effect paradigm to vary the match between incoming and predicted visual stimulation. Participants triggered a bimodal stimulus composed of a Gabor and a tone. The Gabor was either congruent or incongruent compared to an action–effect association that participants learned in an acquisition phase.We tested the influence of action–effect congruency on the loudness perception of the tone. We observed that an incongruent–task-irrelevant Gabor stimulus increases participant’s sensitivity to loudness discrimination. An identical result was obtained for a second condition in which the visual stimulus was predicted by a cue instead of an action. Our results suggest that prediction error is a driving factor of the crossmodal interplay between vision and audition

Detection of regulator genes and eQTLs in gene networks

Genetic differences between individuals associated to quantitative phenotypic traits, including disease states, are usually found in non-coding genomic regions. These genetic variants are often also associated to differences in expression levels of nearby genes (they are "expression quantitative trait loci" or eQTLs for short) and presumably play a gene regulatory role, affecting the status of molecular networks of interacting genes, proteins and metabolites. Computational systems biology approaches to reconstruct causal gene networks from large-scale omics data have therefore become essential to understand the structure of networks controlled by eQTLs together with other regulatory genes, and to generate detailed hypotheses about the molecular mechanisms that lead from genotype to phenotype. Here we review the main analytical methods and softwares to identify eQTLs and their associated genes, to reconstruct co-expression networks and modules, to reconstruct causal Bayesian gene and module networks, and to validate predicted networks in silico.Comment: minor revision with typos corrected; review article; 24 pages, 2 figure

Extensive Copy-Number Variation of Young Genes across Stickleback Populations

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Illusory temporal binding in meditators

We investigate conditions in which more accurate metacognition may lead to greater susceptibility to illusion; and thus conditions under which mindfulness meditation may lead to less accurate perceptions. Specifically, greater awareness of intentions may lead to an illusory compression of time between a voluntary action and its outcome (“intentional binding”). Here we report that experienced Buddhist mindfulness meditators rather than non-meditators display a greater illusory shift of the timing of an outcome towards an intentional action. Mindfulness meditation involves awareness of causal connections between different mental states, including intentions. We argue that this supports improvements in metacognition targeted at motor intentions. Changes in metacognitive ability may result in an earlier and less veridical experience of the timing of action outcomes either through increased access to sensorimotor pre-representations of an action outcome or by affording greater precision to action timing judgements. Furthermore, as intentional binding is an implicit measure of the sense of agency, these results also provide evidence that mindfulness meditators experience a stronger sense of agency